title: Effects of n-3 polyunsaturated fatty acids in the fetal pulmonary circulation.
abstract: OBJECTIVE
  Although evidence exists that n-3 polyunsaturated fatty acids may improve the outcome in patients with severe respiratory failure, little is known regarding their pulmonary circulatory effects. This question is clinically relevant in respiratory failure associated with pulmonary hypertension, in particular in newborn infants with persistent pulmonary hypertension. The objective of this study was to investigate the effects of n-3 polyunsaturated fatty acids on the fetal pulmonary circulation.
  
  
  METHODS
  Randomized, placebo-controlled comparative laboratory investigation.
  
  
  METHODS
  University research facility.
  
  
  METHODS
  Fifty-two chronically prepared lamb fetuses.
  
  
  METHODS
  Catheters and ultrasonic flow transducer were placed through a left thoracotomy in the lamb fetus to determine aortic, pulmonary, and left atrial pressures and left pulmonary artery blood flow.
  
  
  RESULTS
  We compared the pulmonary vascular responses to 120 mins of Omegaven (lipid emulsions enriched in n-3 polyunsaturated fatty acids) or Intralipide (lipid emulsions enriched in n-6 polyunsaturated fatty acids) infusion. Then we investigated the effects of Omegaven on the pulmonary circulation after nitric oxide synthase inhibition by L-nitro-arginine, potassium channel blockade by tetraethylammonium, and cytochrome P450 epoxygenase inhibition by (methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Pulmonary artery and aortic pressures as well as blood gases and plasma lactate concentrations did not change during either fat emulsion infusion. Left pulmonary blood flow increased by 30% and pulmonary vascular resistance decreased by 28% during Omegaven infusion, whereas left pulmonary blood flow and pulmonary vascular resistance did not change during Intralipide infusion. This pulmonary vascular response to Omegaven was not altered by l-nitro-arginine. At the opposite, Omegaven induced pulmonary vasodilatation was abolished by tetraethylammonium and markedly attenuated by (methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide.
  
  
  CONCLUSIONS
  Lipid emulsion containing n-3 polyunsaturated fatty acids may induce a potent and sustained vasodilatation in the fetal lung. This pulmonary vasodilator response is mediated through production of vasoactive mediators by cytochrome P450 epoxygenase and through activation of potassium channels.
authors.affiliation: Pôle de Médecine Périnatale, Hôpital Jeanne de Flandre, CHRU de Lille, Lille, France.
authors.forename: Ali
authors.initials: A
authors.lastname: Houeijeh
authors.forename: Estelle
authors.initials: E
authors.lastname: Aubry
authors.forename: Hélène
authors.initials: H
authors.lastname: Coridon
authors.forename: Karine
authors.initials: K
authors.lastname: Montaigne
authors.forename: Rony
authors.initials: R
authors.lastname: Sfeir
authors.forename: Philippe
authors.initials: P
authors.lastname: Deruelle
authors.forename: Laurent
authors.initials: L
authors.lastname: Storme
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000503:physiopathology; D015221:Potassium Channels / Q000187:drug effects; D011247:Pregnancy; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D015221:Potassium Channels; D003577:Cytochrome P-450 Enzyme System